Lyme disease, due to the spirochete Borrelia burgdorferi, is a major emerging infection in our country. Neurologic involvement has become the significant morbidity of this infection, but has not been well studied. Effective public health poll is being hampered by lack off basic information on clinical and laboratory features and pathogenetic mechanisms of Lyme disease. The objective of this proposal is to identify the frequency, clinical correlate and outcome of central nervous system (CNS) infection in early Lyme disease. This study will focus on 3 adult case groups (N=100) with newly acquired infection: 1) single lesion erythema migrans (EM) (N=25); 2) multifocal EM (N=25); 3) neurologic Lyme disease (N=50). All eligible patient will meet Centers for Disease Control and Prevention diagnostic criteria for Lyme disease. After an initial comprehensive evaluation (self report forms to assess clinical symptoms, psychosocial and psychiatric measures, and health outcome; skin, blood and cerebrospinal fluid (CSF) studies; cognitive assessment) subjects will receive standard antibiotic treatment, and then be followed prospectively for 18 months. Comparison groups will be healthy subjects (N=1 00) frequency matched to cases on age, education and gender; and subjects with other neurologic diseases (N=50). Specific Aim 1: To determine the frequency of CNS invasion in early local and disseminated Lyme disease (invasion will be defined by positive CSF culture, Borrelial antigen, Borrelial DNA, or intrathecal Borrelial antibodies); to document neurologic complaints and health function status of early infection patients. Hypothesis: CNS invasion by B. burgdorferi is common during early infection. Corollary: neurologic complaints are frequent in early Lyme disease. Corollary: in this population new onset of headache is a clinical marker of CNS invasion, while CSF IgM reactivity to B.burgdorferi is an immune marker of CNS invasion. Specific Aim 2: To examine the outcome of neurologic involvement in,early Lyme disease. Hypothesis: Following infection, patients with persistent CSF abnormalities (defined as CNS invasion markers; Borrelial immune complexes; or abnormal cell count or protein) will be symptomatic. Corollary: clearance of CSF is associated with clinical improvement. Specific Aim 3: To determine the proportion of early Lyme disease patients who develop late encephalopathy. Question: what proportion of early Lyme patients will develop persistent neurobehavioral dysfunction in domains of attention and memory? This proposal will help characterize the neurologic aspects of early Lyme disease, will aid in diagnosis and management, and will help guide the formulation of a rational and cost effective health care program for Lyme disease.